Hartlieb, Sabine A., Sieverling, Lina, Nadler-Holly, Michal, Ziehm, Matthias ORCID: 0000-0001-7074-4054, Toprak, Umut H., Herrmann, Carl ORCID: 0000-0003-4989-4722, Ishaque, Naveed ORCID: 0000-0002-8426-901X, Okonechnikov, Konstantin, Gartlgruber, Moritz, Park, Young-Gyu, Wecht, Elisa Maria, Savelyeva, Larissa, Henrich, Kai-Oliver, Rosswog, Carolina, Fischer, Matthias, Hero, Barbara, Jones, David T. W., Pfaff, Elke, Witt, Olaf, Pfister, Stefan M., Volckmann, Richard, Koster, Jan, Kiesel, Katharina, Rippe, Karsten ORCID: 0000-0001-9951-9395, Taschner-Mandl, Sabine ORCID: 0000-0002-1439-5301, Ambros, Peter, Brors, Benedikt ORCID: 0000-0001-5940-3101, Selbach, Matthias, Feuerbach, Lars and Westermann, Frank (2021). Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome. Nat. Commun., 12 (1). BERLIN: NATURE RESEARCH. ISSN 2041-1723

Full text not available from this repository.

Abstract

Telomere maintenance by telomerase activation or alternative lengthening of telomeres (ALT) is a major determinant of poor outcome in neuroblastoma. Here, we screen for ALT in primary and relapsed neuroblastomas (n=760) and characterize its features using multi-omics profiling. ALT-positive tumors are molecularly distinct from other neuroblastoma subtypes and enriched in a population-based clinical sequencing study cohort for relapsed cases. They display reduced ATRX/DAXX complex abundance, due to either ATRX mutations (55%) or low protein expression. The heterochromatic histone mark H3K9me3 recognized by ATRX is enriched at the telomeres of ALT-positive tumors. Notably, we find a high frequency of telomeric repeat loci with a neuroblastoma ALT-specific hotspot on chr1q42.2 and loss of the adjacent chromosomal segment forming a neo-telomere. ALT-positive neuroblastomas proliferate slowly, which is reflected by a protracted clinical course of disease. Nevertheless, children with an ALT-positive neuroblastoma have dismal outcome. Alternative lengthening of telomeres (ALT) is associated with a poor outcome in neuroblastoma. Here, the authors find that ALT is associated with mutated ATRX and/or reduced protein abundance, frequent telomeric repeat loci and heterochromatic telomeric chromatin.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hartlieb, Sabine A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sieverling, LinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nadler-Holly, MichalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziehm, MatthiasUNSPECIFIEDorcid.org/0000-0001-7074-4054UNSPECIFIED
Toprak, Umut H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herrmann, CarlUNSPECIFIEDorcid.org/0000-0003-4989-4722UNSPECIFIED
Ishaque, NaveedUNSPECIFIEDorcid.org/0000-0002-8426-901XUNSPECIFIED
Okonechnikov, KonstantinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gartlgruber, MoritzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park, Young-GyuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wecht, Elisa MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Savelyeva, LarissaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henrich, Kai-OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosswog, CarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hero, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jones, David T. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfaff, ElkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witt, OlafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfister, Stefan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volckmann, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koster, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiesel, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rippe, KarstenUNSPECIFIEDorcid.org/0000-0001-9951-9395UNSPECIFIED
Taschner-Mandl, SabineUNSPECIFIEDorcid.org/0000-0002-1439-5301UNSPECIFIED
Ambros, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brors, BenediktUNSPECIFIEDorcid.org/0000-0001-5940-3101UNSPECIFIED
Selbach, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feuerbach, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westermann, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-601581
DOI: 10.1038/s41467-021-21247-8
Journal or Publication Title: Nat. Commun.
Volume: 12
Number: 1
Date: 2021
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60158

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item